The present invention relates to a new process, which can also be carried out on an industrial scale, for the preparation of 1-substituted 2-methyl-tetrahydropyrimidines from N-substituted propylenediamines and acetoacetic acid esters or acetoacetic acid amides.
A range of other processes for the preparation of 1-alkyl-2-methyl-tetrahydropyrimidines has already been disclosed, such as, for example, the reaction of N-alkylpropylenediamines with open-chain imide-acid esters or amidines (A. Pinner, Die Chemie der Imidoather und ihrer Derivate, (The Chemistry of the Imido-ethers and of their Derivatives), R. Oppenheim, Berlin, 1892), the reaction of N-alkyl-propylenediamine-toluenesulphonic acid salts with carboxylic acid nitriles (J.Chem.Soc. 1947, 497), the hydrogenation of N-acylamino-nitriles, in which the N-acyl-N-alkylpropylenediamines formed are dehydrated under the reaction conditions to give 1-alkyl-2-methyl-tetrahydropyrimidines (J.Am.Chem.Soc. 71, 2350 (1949)) and the reaction of N-alkylpropylenediamines with oxazolines (German Published Specification No. 2,154,948).
However, many of these processes have the disadvantage that the reaction does not take place completely and, in particular, large amounts of undesired by-products are formed. The reaction temperature in these known processes of preparation is throughout 100.degree.- 200.degree. C and the reactions are carried out in the presence of catalysts, for example acid compounds (hydrochloric acid or toluenesulphonic acid) or metal compounds (Ni, Co and Cu).
Further, the reaction of N-ethyl-propylenediamine with acetoacetic acid ethyl ester (Chem. Ber. 98, 3652 (1965)) in the presence of toluenesulphonic acid at reaction temperatures of 210.degree. C is known. This process has been described for an 0.2 molar reaction batch which cannot, however, be extended to industrial scales. Tetrahydropyrimidines, being cyclic amidines, are extremely prone to hydrolysis, so that at the temperature mentioned and in the presence of acid compounds, such as toluenesulphonic acid, the cyclic amidine is immediately saponified by the water formed during the condensation. The N-acyl-N-ethyl-propylenediamine produced by saponification can admittedly be recycled slowly, with elimination of water, under the conditions prevailing in the process of working up by distillation; this recycling is realisable within an entirely acceptable space of time in the case of an 0.2 molar batch, but gives a totally unsatisfactory space-time yield when this process is carried out industrially in batches of 100 kg or more. The working up of the resulting ternary mixture of tetrahydropyrimidine, its saponification product N-acyl-N-alkylpropylenediamine and water proves to be very costly and requires a time-consuming and involved distillation technique. In addition, in consequence of the heat exposure of the reaction mixture, a very high proportion of inutilisable residues is obtained, which substantially lowers the yield of pure product (compare Example 1).